Enhertu secures positive EU panel backing for first pan-tumor HER2 therapy

Enhertu (trastuzumab deruxtecan) moved a step closer to a milestone regulatory approval in Europe, securing a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) as a tumor-agnostic treatment for advanced solid malignancies.

The recommendation positions the targeted therapy to become the first HER2-directed medicine and antibody-drug conjugate (ADC) available for adult patients in the European Union (EU) living with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have progressed on prior therapies and exhaust standard care options.

The asset is being jointly developed and commercialized by AstraZeneca (NYSE:AZN) and Daiichi Sankyo.

The positive opinion will now face final marketing authorization review by the European Commission.

The regulatory endorsement is supported by pooled efficacy data across three Phase 2 clinical trials—DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02—where the ADC demonstrated clinically meaningful, durable responses across multiple distinct cancer types.

In the DESTINY-PanTumor02 trial, which evaluated 111 pretreated patients across various advanced conditions including biliary tract, bladder, cervical, endometrial, ovarian, and pancreatic cancers, Enhertu demonstrated a confirmed objective response rate (ORR) of 51.4% and a median duration of response (DOR) of 14.2 months.

Data from the tumor-specific cohorts further reinforced this pan-tumor activity.

In DESTINY-Lung01, the therapeutic agent achieved a confirmed ORR of 52.9% and a median DOR of 6.9 months among 17 pretreated patients with centrally confirmed HER2-positive non-small cell lung cancer (NSCLC).

Meanwhile, in the DESTINY-CRC02 trial, a 46.9% confirmed ORR and a median DOR of 5.5 months were recorded across 64 pretreated patients with HER2-positive colorectal cancer.

The safety profile of the 5.4 mg/kg dose across these clinical programs remained consistent with prior baseline evaluations, revealing no new safety signals.

Severe hematological and systemic toxicities were monitored across the trials; the most frequent Grade 3 or higher drug-related adverse events in DESTINY-PanTumor02 were neutropenia (10.9%) and anemia (10.9%).

Decreased neutrophil counts (16%) and anemia (7%) were also the prominent Grade 3 or worse toxicities recorded in DESTINY-CRC02.

Special clinical attention remained focused on interstitial lung disease (ILD) or pneumonitis, a known adverse effect associated with the DXd-based ADC platform.

In DESTINY-PanTumor02, ILD occurred in 10.5% of patients, with the vast majority classified as low-grade (Grade 1 or 2), though three fatal Grade 5 events (1.1%) were confirmed by an independent adjudication committee.

In DESTINY-Lung01, the ILD rate stood at 5%, with one initially reported Grade 4 event subsequently adjudicated as a drug-related Grade 5 fatality post-data cutoff.

The DESTINY-CRC02 cohort reported an 8% ILD rate, with all cases restricted to low-grade manifestations.